scholarly journals Properties of repression condensates in living Ciona embryos

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Nicholas Treen ◽  
Shunsuke F. Shimobayashi ◽  
Jorine Eeftens ◽  
Clifford P. Brangwynne ◽  
Michael Levine
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Transcriptional Activators ◽  
Liquid Droplets ◽  
Transcriptional Repressors ◽  
Initiation Complex ◽  
Repressor Proteins ◽  
Liquid Behavior ◽  
Dna Template ◽  
Liquid Liquid Phase Separation

AbstractRecent studies suggest that transcriptional activators and components of the pre-initiation complex (PIC) form higher order associations—clusters or condensates—at active loci. Considerably less is known about the distribution of repressor proteins responsible for gene silencing. Here, we develop an expression assay in living Ciona embryos that captures the liquid behavior of individual nucleoli undergoing dynamic fusion events. The assay is used to visualize puncta of Hes repressors, along with the Groucho/TLE corepressor. We observe that Hes.a/Gro puncta have the properties of viscous liquid droplets that undergo limited fusion events due to association with DNA. Hes.a mutants that are unable to bind DNA display hallmarks of liquid–liquid phase separation, including dynamic fusions of individual condensates to produce large droplets. We propose that the DNA template serves as a scaffold for the formation of Hes condensates, but limits the spread of transcriptional repressors to unwanted regions of the genome.

scholarly journals Perturbation of liquid droplets of P-granule protein LAF-1 by the antimicrobial peptide LL-III

2020 ◽  
Vol 56 (78) ◽  
pp. 11577-11580
Author(s):  
Rosario Oliva ◽  
Sanjib K. Mukherjee ◽  
Zamira Fetahaj ◽  
Simone Möbitz ◽  
Roland Winter
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Antimicrobial Peptides ◽  
Antimicrobial Peptide ◽  
Droplet Formation ◽  
Liquid Phase Separation ◽  
Liquid Droplets ◽  
Cellular Organization ◽  
P Protein ◽  
Liquid Liquid Phase Separation

Protein/RNA droplet formation by liquid–liquid phase separation has emerged as a key mechanism for cellular organization. We show that binding of antimicrobial peptides such as LL-III can lead to loss of droplet function.

scholarly journals Dynamic Formation of Liquid Droplets Triggered by Sequential Enzymatic Reactions

2020 ◽  
Author(s):  
Tomoto Ura ◽  
Shunsuke Tomita ◽  
Kentaro Shiraki
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Enzyme Reaction ◽  
Model System ◽  
Liquid Phase Separation ◽  
Enzymatic Reactions ◽  
Liquid Droplets ◽  
Dynamic Formation ◽  
Liquid Liquid Phase Separation

<p>A model system was developed that dynamically generates two different liquid droplets via liquid–liquid phase separation coupled with a sequential glycolytic reaction. The sequential two-enzyme reaction triggers the formation/dissolution of the liquid droplets. The droplets, in turn, compartmentalize each enzymatic step and generate feedback to accelerate the overall reaction.</p>

MloDisDB: a manually curated database of the relations between membraneless organelles and diseases

2020 ◽  
Author(s):  
Chao Hou ◽  
Haotai Xie ◽  
Yang Fu ◽  
Yao Ma ◽  
Tingting Li
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Biological Processes ◽  
Liquid Droplets ◽  
Nuclear Speckles ◽  
Spatial Regulation ◽  
Temporal And Spatial ◽  
User Friendly ◽  
Functional Factor ◽  
Liquid Liquid Phase Separation

Abstract Cells are compartmentalized by numerous membrane-bounded organelles and membraneless organelles (MLOs) to ensure temporal and spatial regulation of various biological processes. A number of MLOs, such as nucleoli, nuclear speckles and stress granules, exist as liquid droplets within the cells and arise from the condensation of proteins and RNAs via liquid–liquid phase separation (LLPS). By concentrating certain proteins and RNAs, MLOs accelerate biochemical reactions and protect cells during stress, and dysfunction of MLOs is associated with various pathological processes. With the development in this field, more and more relations between the MLOs and diseases have been described; however, these results have not been made available in a centralized resource. Herein, we build MloDisDB, a database which aims to gather the relations between MLOs and diseases from dispersed literature. In addition, the relations between LLPS and diseases were included as well. Currently, MloDisDB contains 771 curated entries from 607 publications; each entry in MloDisDB contains detailed information about the MLO, the disease and the functional factor in the relation. Furthermore, an efficient and user-friendly interface for users to search, browse and download all entries was provided. MloDisDB is the first comprehensive database of the relations between MLOs and diseases so far, and the database is freely accessible at http://mlodis.phasep.pro/.

Dynamic behavior of liquid droplets with enzyme compartmentalization triggered by sequential glycolytic enzyme reactions

2021 ◽  
Author(s):  
Tomoto Ura ◽  
Shunsuke Tomita ◽  
Kentaro Shiraki
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Dynamic Behavior ◽  
Droplet Formation ◽  
Glycolytic Enzyme ◽  
Liquid Phase Separation ◽  
Biological Processes ◽  
Liquid Droplets ◽  
Enzyme Reactions ◽  
Liquid Liquid Phase Separation

Dynamic droplet formation via liquid-liquid phase separation (LLPS) is believed to be involved in the regulation of various biological processes. Here, a model LLPS system coupled with a sequential glycolytic...

A Short Peptide Synthon for Liquid-Liquid Phase Separation

2020 ◽  
Author(s):  
Manzar Abbas ◽  
Wojciech P. Lipiński ◽  
Karina K. Nakashima ◽  
Wilhelm T.S. Huck ◽  
Evan Spruijt
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Living Cells ◽  
Liquid Phase Separation ◽  
Disordered Proteins ◽  
Liquid Droplets ◽  
Short Peptide ◽  
Peptide Analogues ◽  
Single Peptide ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation of disordered proteins has emerged as a ubiquitous route to membraneless compartments in living cells, and similar coacervates may have played a role when the first cells formed. However, existing coacervates are typically made of multiple macromolecular components, and designing short peptide analogues capable of self-coacervation has proven difficult. Here, we present a short peptide synthon for phase separation, made of only two dipeptide stickers linked via a flexible, hydrophilic spacer. These small-molecule compounds self-coacervate into micrometre-sized liquid droplets at sub-mM concentrations, which retain up to 75 weight-% water. The design is general and we derive guidelines for the required sticker hydrophobicity and spacer polarity. To illustrate their potential as protocells, we create a disulphide-linked derivative that undergoes reversible compartmentalisation controlled by redox chemistry. The resulting coacervates sequester and melt nucleic acids, and act as microreactors that catalyse two different anabolic reactions yielding molecules of increasing complexity. This provides a stepping stone for new protocells made of single peptide species.<br>

A Short Peptide Synthon for Liquid-Liquid Phase Separation

2020 ◽  
Author(s):  
Manzar Abbas ◽  
Wojciech P. Lipiński ◽  
Karina K. Nakashima ◽  
Wilhelm T.S. Huck ◽  
Evan Spruijt
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Living Cells ◽  
Liquid Phase Separation ◽  
Disordered Proteins ◽  
Liquid Droplets ◽  
Short Peptide ◽  
Peptide Analogues ◽  
Single Peptide ◽  
Liquid Liquid Phase Separation

Liquid-liquid phase separation of disordered proteins has emerged as a ubiquitous route to membraneless compartments in living cells, and similar coacervates may have played a role when the first cells formed. However, existing coacervates are typically made of multiple macromolecular components, and designing short peptide analogues capable of self-coacervation has proven difficult. Here, we present a short peptide synthon for phase separation, made of only two dipeptide stickers linked via a flexible, hydrophilic spacer. These small-molecule compounds self-coacervate into micrometre-sized liquid droplets at sub-mM concentrations, which retain up to 75 weight-% water. The design is general and we derive guidelines for the required sticker hydrophobicity and spacer polarity. To illustrate their potential as protocells, we create a disulphide-linked derivative that undergoes reversible compartmentalisation controlled by redox chemistry. The resulting coacervates sequester and melt nucleic acids, and act as microreactors that catalyse two different anabolic reactions yielding molecules of increasing complexity. This provides a stepping stone for new protocells made of single peptide species.<br>

scholarly journals Small molecules as potent biphasic modulators of protein liquid-liquid phase separation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
W. Michael Babinchak ◽  
Benjamin K. Dumm ◽  
Sarah Venus ◽  
Solomiia Boyko ◽  
Andrea A. Putnam ◽  
...  
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Small Molecules ◽  
Rational Design ◽  
De Novo ◽  
Liquid Phase Separation ◽  
Disulfonic Acid ◽  
Liquid Droplets ◽  
Small Molecule Modulators ◽  
Liquid Liquid Phase Separation

Abstract Liquid-liquid phase separation (LLPS) of proteins that leads to formation of membrane-less organelles is critical to many biochemical processes in the cell. However, dysregulated LLPS can also facilitate aberrant phase transitions and lead to protein aggregation and disease. Accordingly, there is great interest in identifying small molecules that modulate LLPS. Here, we demonstrate that 4,4’-dianilino-1,1’-binaphthyl-5,5’-disulfonic acid (bis-ANS) and similar compounds are potent biphasic modulators of protein LLPS. Depending on context, bis-ANS can both induce LLPS de novo as well as prevent formation of homotypic liquid droplets. Our study also reveals the mechanisms by which bis-ANS and related compounds modulate LLPS and identify key chemical features of small molecules required for this activity. These findings may provide a foundation for the rational design of small molecule modulators of LLPS with therapeutic value.

scholarly journals Regulatory mechanisms of tau protein fibrillation under the conditions of liquid–liquid phase separation

2020 ◽  
Vol 117 (50) ◽  
pp. 31882-31890
Author(s):  
Solomiia Boyko ◽  
Krystyna Surewicz ◽  
Witold K. Surewicz
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Tau Protein ◽  
Phenotypic Variability ◽  
Total Concentration ◽  
Liquid Phase Separation ◽  
Liquid Droplets ◽  
Tau Isoforms ◽  
Protein Fibrillation ◽  
Liquid Liquid Phase Separation

One of the hallmarks of Alzheimer’s disease and several other neurodegenerative disorders is the aggregation of tau protein into fibrillar structures. Building on recent reports that tau readily undergoes liquid–liquid phase separation (LLPS), here we explored the relationship between disease-related mutations, LLPS, and tau fibrillation. Our data demonstrate that, in contrast to previous suggestions, pathogenic mutations within the pseudorepeat region do not affect tau441’s propensity to form liquid droplets. LLPS does, however, greatly accelerate formation of fibrillar aggregates, and this effect is especially dramatic for tau441 variants with disease-related mutations. Most important, this study also reveals a previously unrecognized mechanism by which LLPS can regulate the rate of fibrillation in mixtures containing tau isoforms with different aggregation propensities. This regulation results from unique properties of proteins under LLPS conditions, where total concentration of all tau variants in the condensed phase is constant. Therefore, the presence of increasing proportions of the slowly aggregating tau isoform gradually lowers the concentration of the isoform with high aggregation propensity, reducing the rate of its fibrillation. This regulatory mechanism may be of direct relevance to phenotypic variability of tauopathies, as the ratios of fast and slowly aggregating tau isoforms in brain varies substantially in different diseases.

scholarly journals FG-nucleoporins caught in the act of liquid–liquid phase separation

2019 ◽  
Vol 219 (1) ◽  
Author(s):  
Dorothee Dormann
Keyword(s):  
Phase Separation ◽  
Liquid Phase ◽  
Barrier Properties ◽  
Liquid Phase Separation ◽  
Nuclear Pore ◽  
Permeability Barrier ◽  
Nuclear Pore Complexes ◽  
Liquid Droplets ◽  
Pore Complexes ◽  
Liquid Liquid Phase Separation

The interior of nuclear pore complexes (NPCs) is densely filled with FG-nucleoporins that form a permeability barrier of a still-obscure nature. Celetti et al. (2019. J. Cell Biol.https://doi.org/10.1083/jcb.201907157) now reveal that FG-nucleoporins can undergo liquid–liquid phase separation and form liquid droplets that mimic permeability barrier properties of intact NPCs.

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